Increased right prefrontal cortical folding in adolescents at risk of schizophrenia for cognitive reasons

Background: Two of the strongest predictors of later schizophrenia in the Edinburgh High Risk Study (EHRS) were the presence of schizotypal features and increased right prefrontal lobe cortical folding. We examined the association between these measures in adolescents at enhanced risk of developing schizophrenia due to cognitive impairment.

Methods: One hundred forty-three adolescents receiving special education were divided into two groups using the cut-off on the Structured Interview for Schizotypy (SIS) which optimally predicted later schizophrenia in the EHRS. Each participant received a structural magnetic resonance imaging scan. Prefrontal tissue volumes and a standard measure of cortical folding, the gyrification index (GI), were determined automatically using automated (A)-GI methodology.

Results: Those who scored above the SIS cut-off had a significantly higher right prefrontal lobe GI compared to those below the cut-off (F = 4.72, p =.03). GI correlated strongly with prefrontal tissue volumes, although when prefrontal volume was added as a covariate to the GI analysis a trend towards a group difference remained evident.

Conclusions: The level of schizotypal cognitions among adolescents with cognitive impairment identifies a group with the same pattern of cortical folding seen in those with familial risk factors who later develop the disorder. Increased right prefrontal GI may reflect disordered connectivity in individuals with the greatest risk of developing schizophrenia.